Clinical Trial Results:
Open, non-controlled, multicentre, first-in-man study using escalating doses of LFB-R603 in patients with advanced stage B-Chronic lymphocytic leukemia.
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Summary
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EudraCT number |
2008-002601-40 |
Trial protocol |
FR |
Global end of trial date |
23 Aug 2011
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Dec 2016
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First version publication date |
31 Dec 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CD20-0703
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
LFB Biotechnologies
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Sponsor organisation address |
3 Avenue des Tropiques, COURTABOEUF, France, 91953
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Public contact |
Global Clinical Development Leader, LFB Biotechonologies, 33 169825656,
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Scientific contact |
Global Clinical Development Leader, LFB Biotechonologies, 33 169825656,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Apr 2012
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Aug 2011
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Aug 2011
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective is to assess the safety of LFB-R603 administered to patients suffering from advanced B-CLL, relapsed or refractory after at least one prior course of fludarabin.
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Protection of trial subjects |
The Safety Committee was due to meet systematically within a maximum of 24 hours before each new cohort began treatment to analyse all potential AEs/SAEs and review, if necessary, the recommendations made during the previous meeting(s).
The Safety Committee made recommendation whether or not it was possible to escalate the dose to a higher dose level as per the dose administration rules.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Nov 2008
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
12 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 33
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Worldwide total number of subjects |
33
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EEA total number of subjects |
33
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
18
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From 65 to 84 years |
15
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85 years and over |
0
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Recruitment
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Recruitment details |
Of the 41 patients screened between November 2008 and September 2010, 33 were eligible (IS population) and received treatment (TTS population); 21 in Part I: 6 at 75 mg, 3 each at 200 mg, 510 mg, 1050 mg, 6 at 1650 mg; 12 in Part II at 3300 mg. | ||||||||||||||||
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Pre-assignment
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Screening details |
- | ||||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
41 [1] | ||||||||||||||||
Number of subjects completed |
33 | ||||||||||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
screening failure: 8 | ||||||||||||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Of the 41 patients screened between November 2008 and September 2010, 33 were eligible and were enrolled in the trial. |
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Period 1
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Period 1 title |
Baseline period
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Total Patients | ||||||||||||||||
Arm description |
A total of 33 patients were included to receive study treatment, 21 in the Part I dose escalation phase (75 mg to 1650 mg) and 12 in Part II (3300 mg). An additional patient was included in Part II compared to the 11 planned inclusions due to concomitant inclusion processes in two Investigational Centres. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
LFB-R603
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Investigational medicinal product code |
anti-CD20
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Part I:
Five consecutive cohorts of 3 to 6 patients were planned. In each cohort, patients received once weekly infusions of LFB-R603 for 4 weeks at doses ranging from 5 to 450 mg as follows:
Cohort A: 5 mg, 10 mg, 20 mg and 40 mg for infusions 1, 2, 3 and 4, respectively
Cohort B: 20 mg for the 1st infusion and 60 mg for the next 3 infusions
Cohort C: 60 mg for the 1st infusion and 150 mg for the next 3 infusions
Cohort D: 150 mg for the 1st infusion and 300 mg for the next 3 infusions
Cohort E: 300 mg for the 1st infusion and 450 mg for the next 3 infusions
Part II:
Cohort F: 12 patients received once- weekly infusions of LFB-R603 for 8 weeks. For each patient, the first dose was 150 mg and each subsequent dose (from 2 to 8) was 450 mg.
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Period 2
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Period 2 title |
Treatment period
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Is this the baseline period? |
No | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Total Patients | ||||||||||||||||
Arm description |
A total of 33 patients were included to receive study treatment, 21 in the Part I dose escalation phase (75 mg to 1650 mg) and 12 in Part II (3300 mg). An additional patient was included in Part II compared to the 11 planned inclusions due to concomitant inclusion processes in two Investigational Centres. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
LFB-R603
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Investigational medicinal product code |
anti-CD20
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Part I:
Five consecutive cohorts of 3 to 6 patients were planned. In each cohort, patients received once weekly infusions of LFB-R603 for 4 weeks at doses ranging from 5 to 450 mg as follows:
Cohort A: 5 mg, 10 mg, 20 mg and 40 mg for infusions 1, 2, 3 and 4, respectively
Cohort B: 20 mg for the 1st infusion and 60 mg for the next 3 infusions
Cohort C: 60 mg for the 1st infusion and 150 mg for the next 3 infusions
Cohort D: 150 mg for the 1st infusion and 300 mg for the next 3 infusions
Cohort E: 300 mg for the 1st infusion and 450 mg for the next 3 infusions
Part II:
Cohort F: 12 patients received once- weekly infusions of LFB-R603 for 8 weeks. For each patient, the first dose was 150 mg and each subsequent dose (from 2 to 8) was 450 mg.
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Period 3
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Period 3 title |
follow-up period
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Is this the baseline period? |
No | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Total Patients | ||||||||||||||||
Arm description |
A total of 33 patients were included to receive study treatment, 21 in the Part I dose escalation phase (75 mg to 1650 mg) and 12 in Part II (3300 mg). An additional patient was included in Part II compared to the 11 planned inclusions due to concomitant inclusion processes in two Investigational Centres. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
LFB-R603
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Investigational medicinal product code |
anti-CD20
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
No administration during follow-up period.
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Baseline characteristics reporting groups
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Reporting group title |
Baseline period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Part I
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||
Subject analysis set description |
subjects included in the Part I
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Subject analysis set title |
part II
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subjects included in the part II
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End points reporting groups
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Reporting group title |
Total Patients
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Reporting group description |
A total of 33 patients were included to receive study treatment, 21 in the Part I dose escalation phase (75 mg to 1650 mg) and 12 in Part II (3300 mg). An additional patient was included in Part II compared to the 11 planned inclusions due to concomitant inclusion processes in two Investigational Centres. | ||
Reporting group title |
Total Patients
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Reporting group description |
A total of 33 patients were included to receive study treatment, 21 in the Part I dose escalation phase (75 mg to 1650 mg) and 12 in Part II (3300 mg). An additional patient was included in Part II compared to the 11 planned inclusions due to concomitant inclusion processes in two Investigational Centres. | ||
Reporting group title |
Total Patients
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Reporting group description |
A total of 33 patients were included to receive study treatment, 21 in the Part I dose escalation phase (75 mg to 1650 mg) and 12 in Part II (3300 mg). An additional patient was included in Part II compared to the 11 planned inclusions due to concomitant inclusion processes in two Investigational Centres. | ||
Subject analysis set title |
Part I
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
subjects included in the Part I
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Subject analysis set title |
part II
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Subjects included in the part II
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End point title |
adverse events occurrence [1] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: descriptive analysis. |
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
Throughout the study.
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Adverse event reporting additional description |
TEAEs reporting below occured in ≥4 patients.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.1
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Reporting groups
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Reporting group title |
Total Patients
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Reporting group description |
A total of 33 patients were included to receive study treatment, 21 in the Part I dose escalation phase (75 mg to 1650 mg) and 12 in Part II (3300 mg). An additional patient was included in Part II compared to the 11 planned inclusions due to concomitant inclusion processes in two Investigational Centres. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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17 Dec 2008 |
- To notify a change in a prohibited prior and/or concomitant medication. Prior and concomitant IV or subcutaneous immunoglobulin infusion was prohibited during the study treatment. However, since LFB-R603 may increase the risk of infections, especially serious bacterial infections in this selected population of patients, the use of IV or subcutaneous immunoglobulins was authorised if deemed necessary for patient's welfare.
- To notify a correction made in the flow rate of administration for infusions 3 and 4 of LFB-R603.
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20 Jan 2009 |
To specify the modality of administration of LFB-R603. For the dose between 5 and 150 mg, in order to maintain the permeability during the infusion, a concomitant administration of NaCl 0.9% was recommended. |
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07 May 2009 |
- To specify the wash-out period of any other medication for CLL required prior to study entry.
- To specify that progression of the disease was to be evaluated according to the NCI-WG criteria 2008.
- To add premedication with methylprednisolone for infusions 3 and 4 of LFB-R603 in all cohorts.
- To extend the duration of Part I of the study from 7.5 months to 10 months and to delay the first patient in Part II.
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14 Aug 2009 |
- To notify the change in the modality of administration of LFB-R603 infusion. |
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28 Jan 2010 |
-To notify the recommended dose escalation regimen to be used in Part II of the study.
- To specify the total of 11 additional patients were to be treated in part II in order to determine the recommended dose for subsequent clinical trials.
- To specify the role of the Safety Committee in Part II of the study.
- To add a thoracic, abdominal and pelvic CT-scan at M2 in order to evaluate the tumour burden and assess the relationship between tumour burden and lymphocyte depletion.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
